X-连锁无丙种球蛋白血症3例报告并文献复习

Three cases report and literature review of X-Linked agammaglobulinemia

目的分析X-连锁无丙种球蛋白血症(XLA)的临床表现、诊断和治疗特点。方法回顾性分析3例XLA患儿的临床特点、细胞免疫、体液免疫指标及治疗和预后。结果 3例XLA患儿的发病年龄自11个月至6岁,中位诊断年龄为12岁。患儿均表现为多发反复细菌感染;关节炎症累及膝、踝、肘和髋等大关节。实验室检查提示血清免疫球蛋白水平及循环B细胞明显降低。3例患儿均发现存在BTK基因突变,分别为外显子3的移码突变及无义突变,外显子10的移码突变,以及外显子18的错义突变。确诊为XLA后予静脉滴注丙种球蛋白(IVIG)替代治疗;合并关节炎加用非甾体类抗炎药物(NSAIDs),酌情加用小剂量激素,病情得到明显改善。结论 XLA临床表现具有较大的变异性,反复不同部位的细菌感染,扁桃体、淋巴结发育不良及血清免疫球蛋白水平低下是早期诊断XLA的重要环节;XLA合并关节炎使用IVIG和NSAIDs联合治疗,谨慎使用激素或免疫抑制剂。

Objective To analyze the clinical features, diagnosis and treatment of X-Linked Agarnmaglobulinemia （XLA）. Methods Clinical features, cellular and humoral immune functions, treatment and prognosis from 3 patients with XLA were retrospectively reviewed. Results The age of onset were from 11 months to 6 years in these 3 cases, however, the median age of diagnosis was 12 years. All patients showed multiple recurrent bacterial infections, arthritis involved large joints such as knee, ankle, elbow and hip. Laboratory examination revealed the decrease of serum gammmaglohulin and absence of B lymphocytes in the peripheral blood. All 3 patients were identiifed BTK mutations, which were frameshift mutation and nonsense mutation in exon 3, frameshift mutation in exon 10, missense mutation in exon 18. After XLA was diagnosed, the patients were managed by intravenous gammagloulin （IVIG） replacement. The non-steroidal anti-inflammatory drugs （NSAIDs） were administrated in patients combined arthritis. The small dose of hormones had been applied. All patients had a significantly improvement. Conclusions The clinical features of XLA have greater variability, with recurrent bacterial infections. Markedly decreased and absent tosils and lymph nodes, serum immunoglobulin may be one of the warning signs for early diagnosis of XLA. IVIG and NSAIDs can be jointly treatment of XLA with arthritis. The steroid and immunosuppressant agents should be used with caution.